Targeted STING Activation Using Modified Ultrasound-Responsive Microbubbles Enhances Immune Checkpoint Blockade Against Melanoma

Authors

Sina Khorsandi
Kristin Huntoon
Yifan Wang
Adam Woodward
Abin Antony
Connor Endsley
Nazia Hafeez
Jared L Edwards
Nicole McCuen
Prasanna G Alluri
Betty Y S Kim
Wen Jiang
Jacques Lux

Publication Date

6-1-2025

Journal

Advanced Science

DOI

10.1002/advs.202416596

PMID

40135812

PMCID

PMC12165055

PubMedCentral® Posted Date

3-26-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Despite the recent successes of immune checkpoint inhibitors (ICIs) in treating advanced melanoma, durable clinical responses still remain limited. To boost immune responses, agents that target immune regulators, such as the Stimulator of Interferon Genes (STING) agonist cyclic GMP-AMP (cGAMP), are being investigated. However, their clinical translation is impeded by poor serum stability, rapid tissue clearance, and T-cell death due to off-target activation. Recently, a novel strategy termed Microbubble-assisted UltraSound-guided Immunotherapy of Cancer (MUSIC) has been reported to selectively deliver cGAMP directly into the cytosol of antigen-presenting cells with spatiotemporal control. The resulting activation of STING and downstream proinflammatory pathways produces antitumor effects in murine models of breast cancer. Herein, this study reports that MUSIC provides curative results in aggressive murine models of melanoma as well. Under ultrasound exposure, MUSIC reduces tumor size, increases overall survival, and synergizes with ICIs to bridge innate and adaptive immunities. The results from this study represent MUSIC's ability to produce potent immune responses in melanoma, thus indicating its potential as an adjuvant for cancers where ICI is the current standard of care.

Keywords

Animals, Immune Checkpoint Inhibitors, Mice, Microbubbles, Melanoma, Immunotherapy, Membrane Proteins, Female, Nucleotides, Cyclic, Mice, Inbred C57BL, Disease Models, Animal, Ultrasonography, Cell Line, Tumor, Melanoma, Experimental, cancer therapy, drug delivery, immunotherapy, microbubbles, sting pathway, ultrasound

Published Open-Access

yes

Recommended Citation

Khorsandi, Sina; Huntoon, Kristin; Wang, Yifan; et al., "Targeted STING Activation Using Modified Ultrasound-Responsive Microbubbles Enhances Immune Checkpoint Blockade Against Melanoma" (2025). Faculty, Staff and Student Publications. 4550.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4550